Project Summary/Abstract Air pollution is associated with a range of health outcomes; while historically, the focus has been on cardiopulmonary effects, recent toxicological and epidemiologic evidence indicates neurotoxic effects, especially of particulate matter (PM). Pre- and post-natal exposure to PM has been associated with adverse child neurodevelopmental outcomes, though important questions regarding critical windows of exposure remain unanswered. Given the developmental potential of children (in addition to the fetus), exposure timing is critical in determining the specific nature of exposure-outcome relationships. Lack of detailed exposure data (e.g., multiple individual-level exposure estimates over the life course) in large pediatric cohort studies hinders efforts to define the complex interplay of factors that determine child health and carefully examine hypotheses related to critical windows of susceptibility to environmental exposures. While in utero exposure to PM may have a direct effect on child neurodevelopmental outcomes, it is possible that this effect is moderated by (or in the case of prenatal exposures mediated through and moderated by) in utero fetal growth. Thus far, the role of fetal growth in child neurodevelopment has been largely based on studies in children born preterm or small-for-gestational age (SGA). While convenient and low cost, measures at birth do not capture the dynamic nature of fetal growth. Additionally, anthropometric measures at birth provide a particularly poor proxy of fetal growth during early pregnancy, which may be an important period of exposure for many environmental contaminants, such as air pollution. The primary goal of the proposed study is to evaluate critical windows of exposure to PM with aerodynamic diameter < 2.5 microns (PM2.5) on child cognitive function and behavioral outcomes at ages four and seven and the secondary goal of this study is to gain a better understanding of the role of fetal growth, and head growth in particular, in the causal pathway linking PM2.5 to child neurodevelopment. This study will be conducted among children from the INMA (Spanish INfancia y Medio Ambiente) project, a network of birth cohorts in Spain. INMA is unique in includes extensive standardized and objective measures of child neurocognitive and behavioral outcomes at multiple time points, serial indicators of fetal growth (at least three ultrasounds per woman) and extensive residential and health histories. Many of these data are unavailable in other large childhood cohorts. Given rapid development during fetal development, infancy and early childhood, a more complete understanding of the mechanism through which pre- and postnatal air pollution exposures affect child neurodevelopment, as well as potential windows of susceptibility, may inform interventions aimed at reducing early exposures and ultimately decreasing disease burden. I propose capitalizing on a wealth of data collected in an established pregnancy cohort, utilizing new approaches for assessment and evaluation of estimates of individual residential PM2.5 exposures, and applying novel statistical methods to identify critical windows of susceptibility to PM2.5. This study will address gaps that present critical barriers to our ability to translate models of child health into strategies for pediatric health promotion and disease prevention.